Attention
This section of the web-site contains information on medicines, advertising of which is not foreseen by the legislation. Information in this section is intended for reference only, has exclusively scientific and informative character and should not be treated as advertising information for a wide range of people. According to the current legislation, access to this information is granted to medical and pharmaceutical employees. Please confirm that you are a medical or pharmaceutical employee.

PK-Merz tablets

Indications:

Parkinson's syndrome: treatment of Parkinson's disease symptoms, such as rigidity, tremor, hypokinesia and akinesia. Extrapyramidal side effects of neuroleptics and other drugs: early dyskinesia, akathisia and parkinsonism.

Pharmacodynamics. Amantadine has diverse pharmacological properties. It is an indirect agonist of striatal dopamine receptor. Animal studies have shown that amantadine increases extracellular dopamine concentration both by increased dopamine release and by inhibiting reuptake in presynaptic nerve cells. In therapeutic dosages, amantadine inhibits NMDA- receptors mediated release of acetylcholine, and thus may have anticholinergic effects. Amantadine exerts synergistic effect with L-DOPA.

Pharmacokinetics. Amantadine is rapidly and completely absorbed in the GIT after oral administration. Maximum concentration (Cmax) in plasma is reached in 2-8 hours after a single dose. With administration of medication at a dose of 200 mg/day, steady state concentration is achieved after 4-7 days at 400-900 ng/ml plasma concentration. After administration of 100 mg of amantadine sulphate Cmax makes 0.15µg/ml.

Plasma clearance is defined as equal to the kidney one and makes 17.7 ± 10 l/h in healthy adult volunteers. Apparent volume of distribution (4.2 ± 1.9 l/kg) depends on the age; in adult humans it makes 6 l/kg.

The half-life (T½) is 10-30 hours (15 hours on average) and is largely dependent on the patient’s age. In older men (62-72 years) T½ is 30 hours. In patients with renal failure final T½ from plasma can be significantly lengthened (to 68 ± 10 h).

Upon infusion of 200 mg of amantadine sulphate, Cmax after 3 hours makes 0.54 µg/ml. After the treatment at a dose of 200 mg/day, an average plasma concentration of 0.76 µg/ml is reached at the end of infusion, on Day 6. An average total clearance was calculated at 3.6 l/h; T½ from plasma ranges from 7 to 23 hours with a mean of about 10 hours.

Amantadine binds to plasma proteins by nearly 67% (in vitro); nearly 33% are found unbound in plasma. It passes through blood-brain barrier (BBB) using saturable transport systems.

Amantadine is excreted via urine almost unchanged (90% of a single dose); a small amount is excreted via feces.

Amantadine has low dialysis capacity – nearly 5% per dialysis. Amantadine is not metabolized in human body.

Orally, to adults.

Tablets should be taken with a small amount of fluids, preferably in the morning and in the afternoon. It is not recommended to take the last daily dose later than 4 pm.

Single and daily doses. Provided for the adherence to aforementioned precautions and contraindications, you may prevent such life-threatening side effect as chaotic polymorphic ventricular tachycardia.

The treatment of patients with Parkinson's syndrome and impaired motor activity caused by administration of other medications should be done gradually, following the dosing defined for the therapeutic effect.

It is recommended to start treatment with 1 tablet (100 mg of amantadine sulphate) per day during the first 4-7 days with a further increase of the daily dose to 1 tablet 1 time a week to achieve efficient therapeutic dose.

Usual effective dose is 1-3 tablets 2 times a day (200-600 mg of amantadine sulphate).

Daily dose for elderly patients with agitation, confusion or delirium syndromes makes 100 mg (1 tablet). If this dose is ineffective, it may be gradually increased to 200 mg/day under strict doctor’s supervision.

In case of combination treatment with other anti-Parkinsonian agents, the dose should be defined individually.

For patients who have previously been treated with amantadine injection solution, initial dose should be higher.

marked aggravation of Parkinson’s disease symptoms i.e. in akinetic crisis, it is advised to administer amantadine sulphate solution.

Doses for patients with renal failure.

Doses for patients with renal failure should be adjusted in line with glomerular filtrate rate (GFR) as shown in table below:

 

GFR, ml/min

Amantadine sulphate dose, mg

Dose interval

80–60

100

Every 12 hours

60–50

200 and 100*

Every following day*

50–30

100

1 time per day

30–20

200

2 times per day

20–10

100

3 times per day

<10 and hemodialysis patients

200 and 100

1 time per week or 1 time every 2 weeks

 

*The dose is achieved by infusion of 100 mg and 200 mg, one after another or intake of 100 mg (1 tablet a day) and 200 mg (2 tablets a day) one after another.

GFR can be roughly defined under the following equation:
Clcr = (140 — age) х body weight / 72 х creatinine,
where:
Clcr = creatinine clearance in ml/min and creatinine = serum creatinine in mg/100 ml.

Creatinine clearance defined under this equation is exclusively concerned with men (corresponding value for women is 85% of the current value) and can be compared to inulin clearance used to determine GFR (120 ml/min for adults).

Amantadine is characterized by low dialyzing (about 5%).

The course of treatment depends on the nature and severity of the disease and is determined by your doctor. Patients should not discontinue treatment on their own. It is recommended to avoid abrupt discontinuation of medication, otherwise patients with Parkinson's disease may experience increased extrapyramidal symptoms that sometimes induce akinetic crisis, and furthermore, discontinuation may result in delirium.

Composition:

 

1 tablet contains:
Amantadine sulphate 100 mg

 

Other ingredients: lactose monohydrate, microcrystalline cellulose, farina, gelatin, povidone, talc, magnesium stearate, anhydrous colloidal silicon dioxide, cross-carmellose sodium,  butyl methacrylate -(2-dimethylaminoethyl) - methacrylate - metilmethacrylate copolymer (1: 2: 1), Orange Yellow S, titanium dioxide pigment.

Pharmacotherapeutic group: Anti-Parkinsonian medications. ATC code: N04B B01.

Indications:

Tablets:
Parkinson's syndrome: treatment of Parkinson's disease symptoms, such as rigidity, tremor, hypokinesia and akinesia. Extrapyramidal side effects of neuroleptics and other drugs: early dyskinesia, akathisia and parkinsonism.

Contraindications:

  • hypersensitivity to amantadine or other ingredients;
  • decompensated heart failure (NYHA IV stage);
  • cardiomyopathy and myocarditis;
  • II and III type atrioventricular heart block;
  • bradycardia (less than 55 b.p.m.);
  • family history of prolonged Q-T interval (Bazett Q-Tc> 420 ms) or with prominent U-waves, or with congenital Q-T-syndrome;
  • severe ventricular arrhythmia, to include chaotic polymorphic ventricular tachycardia;
  • simultaneous treatment with Budipine or other drugs prolonging Q-T interval (see INTERACTIONS);
  • low content of potassium or magnesium in blood.

Side effects:

 

Very common >1/10
Common >1/100, <1/10
Uncommon >1/1000, <1/100
Rarely >1/10 000, <1/1000
Very rarely <1/10 000, to include individual reports

 

Psychiatric disorders. Common: sleep disturbance and mental agitation. Patients (especially elderly) who are predisposed to mental disorders may experience paranoid exogenous psychoses accompanied by visual hallucinations. These side effects may be more frequent if medication is co-taken with other anti-Pakinsonian drugs (e.g. L-DOPA, Bromocriptin or Memantinum).

Nerve system.
Common: aggravation of motor symptoms.
Uncommon: dizziness, orthostatic disorders.
Rarely: blurred vision.
Very rarely: cerebral seizures, usually after overdosed treatment, myoclonia and peripheral neuropathy symptoms.

Visual disorders. Very rarely: flash blindness.

Heart disturbances. Very rarely: cardiac arrhythmia (ventricular tachycardia, ventricular fibrillation, chaotic polymorphic ventricular tachycardia and QT interval elongation). The majority of these cases were caused by overdosage, concomitant intake of particular drugs or other risk factors (see CONTRAINDICATIONS and INTERACTION).

Vascular disorders. Common: marbled skin accompanied by swelling of the lower leg and ankle.

Digestive tract. Uncommon: nausea, dry mouth.

Cutaneous and subcutaneous disorders. Very rarely: increased photosensitivity.
Infusion therapy with PK-Merz may cause allergic reactions. Orange-Yellow S (E110) contained in the medication may cause allergic reactions.

Urogenital system. Common: retention in patients with prostatic hypertrophy.

Interactions:
Before co-administration of any other medicines with PK-Merz, you should carefully read package leaflet in order to find out about amantadine interaction with these medications, which may result in elongation of Q-T interval.
The medication may be applied together with other anti-Parkinsonian agents. To avoid side effects (such as psychotic reactions) it is advised to lower the dose of other drugs or combinations thereof.
Special studies on PK-Merz interaction with other anti-Parkinsonian agents (e.g., L-DOPA, Bromocriptinum, Memantinum and Trihexyphenidyl) were not conducted (see SIDE EFFECTS).
Co-intake of PK-Merz with any other groups of medications or active ingredients listed below may result in the following interactions:
Anticholinergics. Aggravation anticholinergics (e.g. Trihexyphenidyl, Benzatropine, Scopolamine, Biperiden, Orphenadrine etc.) side effects (confusion and hallucinations).
Sympathomimetic dugs with direct action on the CNS. Aggravation of major amantadine effect.
Alcohol. Reduced alcohol tolerance.
L-DOPA (anti-Parkinsonian drug). Mutual enhancement of therapeutic effect. Therefore, L-DOPA may be administered together with PK-Merz.
Other anti-Parkinsonian agents. Memantinum may aggravate PK-Merz action and its side effects (pay special attention to SPECIAL GUIDELINES).
Other medications.
Co-administration of diuretics, such as Triamterenum/Hydrochlorothiazidum, can slow down amantadine removal from blood plasma, which leads to a toxic concentration of the latter in blood plasma. Therefore, you should avoid co-administration of this combination.
Co-administration of amantadine with other QT interval elongating drugs is also counterindicated. These include:

  • >particular class IA (e.g. Chinidunum, Disopyramidum, Procainamidum) and class III (e.g. Amiodaronum, Sotalol) antiarrhythmic agents;
  • particular antipsychotics (e.g. Thioridazinum, Chlorpromazinum, Haloperidolum, Pimozid);
  • particular tricyclic and tetracyclic antidepressants (e.g. Amitriptylinum);
  • particular antihistamines (e.g. Astemizole, Terfenadinum);
  • particular macrolide antibiotics (e.g. Erythromycinum, Clarithromycin);
  • particular gyrase inhibitors (e.g. Sparfloxacinum);
  • azole antifungals and other drugs such as Budipine, Halofantrine, Co-trimoxazole, Pentamidine, Cisapridum and Bepridil.

Alcohol aggravates medication side effects.

Overdosage:
Symptoms. Acute intoxication characterized by nausea, vomiting, excitement, tremors, ataxia, blurred vision, lethargy, depression, dysarthria and convulsions; cardiac arrhythmia.
Acute toxic psychosis in the form of confusion with visual hallucinations, sometimes with coma and myoclonus, was observed after co-intake of amantadine and other anti-Parkinsonian drugs.
Treatment. Special medical treatment or antidote is unknown. In case of PK-Merz intoxication, you should induce vomiting and/or gastric lavage. Besides, it is necessary to take related therapeutic measures that include administration of fluid and acidification of urine to rapidly remove medication, sedation and anti-convulsion and anti-arrhythmia measures.
To remove neurotoxic symptoms you may administer 1-2 mg of Physostigminum I.V. every 2 h to adults and 2 x 0.5 mg at 5-10 minutes interval to children until reaching maximum dose of 2 mg.
It is recommended to specifically watch over the patients susceptible to a possible elongation of Q-T interval and to factors contributing to the emergence of chaotic polymorphic ventricular tachycardia, such as electrolyte imbalance (hypokalemia and hypomagnesemia, in particular) or bradycardia.
Due to the low amantadine capacity to dialysis (about 5%) hemodialysis is not recommended.

Patients, who take neuroleptics together with PK-Merz, are at risk of malignant neuroleptic syndrome in case they suddenly discontinue PK-Merz. Patients with renal disease may experience toxicity.

One should be particularly careful when prescribing the medication to patients with organic brain syndrome or patients with epileptic seizures, since aggravation of individual symptoms may be observed (see ADMINISTRATION and SIDE EFFECTS).

Patients with known cardiovascular disorders should be under constant medical supervision during PK-Merz treatment.

Patients with Parkinson's disease often have such symptoms as hypotension, increased salivation, sweating, fever, edema and depression. These patients need to pay special attention to PK-Merz side effects and its interaction with other drugs.

Patients should inform their physician in case of difficulties with urination.

500 ml dropper with infusion solution contains 77 mmol of sodium (1770 mg of sodium). This should be taken into account in relation to low-salt diet patients.

Special precautions should be taken, when assigning the medication to patients with:

  • prostatic hypertrophy;
  • narrow-angle glaucoma;
  • renal failure (of diverse severity; there is a risk of amantadine accumulation due to the worsening of renal filtration (see ADMINISTRATION);
  • agitation or mental confusion;
  • the history of delirium syndrome or exogenous psychosis;
  • Memantunum co-treatment (see INTERACTIONS).

Before and after 1 and 3 weeks of treatment it is necessary to make ECG (50 mm/sec) and Bazett correction of Q-T (Q-Tc), which is defined manually. Such ECG should be carried out before any further increase in the dose and 2 weeks after it. Later ECG should be made at least one time per year. The treatment should not be started or should be discontinued if the initial value of Q-Tc is> 420 ms, with Q-T increase by more than 60 ms during drug treatment, or if Q-Tc is> 480 ms, as well as in patients with visible U-waves on ECG.

Patients at risk of electrolyte unbalance that may, e.g., be caused by the treatment with diuretics, those experiencing frequent vomiting and/or diarrhea, patients using insulin in emergency situations or patients with renal or anorectic disorders should undergo testing and monitoring of laboratory parameters, as well as related replenishment of electrolytes, especially potassium and magnesium.

Should such symptoms as palpitations, dizziness or syncope manifest during PK-Merz treatment, the latter should be stopped immediately and the patient should be under 24 hours supervision as related to Q-T interval elongation. If there is no Q-T elongation, one may resume drug treatment, taking into account contraindications and interactions. In patients with cardiac pacemaker, exact determination of Q-T interval is not possible, therefore the decision as to the use of PK-Merz should be taken individually and on the cardiologist’s advice.

Additional administration of amantadine to prevent and treat influenza caused by A virus is not recommended due to the overdose risk.

Use in pregnancy and breastfeeding: during pregnancy, the medication may be administered only after thorough assessment of fetus’s risk/mother’s benefit ratio. There is not data on penetration of medication into placenta. Also there is no adequate data on amantadine application in pregnant women. In animal studies, amantadine has shown embryotoxic and teratogenic effects. The potential risk for humans is unknown.

Thus, in case of emergency, amantadine can be used during pregnancy. If therapy is conducted in the Ist trimester, ultrasound investigation should be made. If amantadine is prescribed to a woman of childbearing age, the patient, in case of suspected or assumed pregnancy, should be instructed to seek medical advice.

Use in breastfeeding period: PK-Merz passes into the breast milk. If amantadine is required during lactation, it is necessary to keep watch over the child for the subject of possible symptoms associated with drug administration (skin rash, urinary retention, vomiting); breastfeeding should be discontinued.

Effects on ability to drive vehicles or use other mechanisms: given possible medication side effects on the CNS it is advised to refrain from driving and operating any other mechanisms during its intake.

Use in children: there is no any data on the use of medication in children; therefore it is not applied in this age group of patients.

Storage requirements: Keep out of the reach of children and at up to 25°С temperature.

Shelf life: 5 years.

Dispensing method: on prescription.

1

Ask a question

To prevent automated spam submissions leave this field empty.